Structural basis for loading and inhibition of a bacterial T6 SS phospholipase effector by the VgrG spike
Language
EN
Article de revue
This item was published in
EMBO Journal. 2020-06-02, vol. 39, n° 11, p. e104129
English Abstract
The bacterial type VI secretion system (T6SS) is a macromolecular machine that injects effectors into prokaryotic and eukaryotic cells. The mode of action of the T6SS is similar to contractile phages: the contraction of a ...Read more >
The bacterial type VI secretion system (T6SS) is a macromolecular machine that injects effectors into prokaryotic and eukaryotic cells. The mode of action of the T6SS is similar to contractile phages: the contraction of a sheath structure pushes a tube topped by a spike into target cells. Effectors are loaded onto the spike or confined into the tube. In enteroaggregative Escherichia coli, the Tle1 phospholipase binds the C-terminal extension of the VgrG trimeric spike. Here, we purify the VgrG-Tle1 complex and show that a VgrG trimer binds three Tle1 monomers and inhibits their activity. Using covalent cross-linking coupled to high-resolution mass spectrometry, we provide information on the sites of contact and further identify the requirement for a Tle1 N-terminal secretion sequence in complex formation. Finally, we report the 2.6-Å-resolution cryo-electron microscopy tri-dimensional structure of the (VgrG) 3-(Tle1) 3 complex revealing how the effector binds its cargo, and how VgrG inhibits Tle1 phospholipase activity. The inhibition of Tle1 phospholipase activity once bound to VgrG suggests that Tle1 dissociation from VgrG is required upon delivery.Read less <
English Keywords
type VI secretion system
Structural Biology
Virology & Host Pathogen Interaction
type VI secretion system Subject Categories Microbiology
protein secretion
cryo-electron microscopy
bacterial toxin
bacterial competition
European Project
Infrastructure for NMR, EM and X-ray crystallography for translational research
ANR Project
Contribution des Effecteurs du Système de Sécrétion de Type VI à la pathogénicité des Escherichia coli adhérents-invasifs
Guerre bactérienne: Architecture et Fonction du Système de Sécrétion de Type VI - ANR-14-CE14-0006
Bloc-outil et Imagerie de Précision pour le Binage Intra-rang Précoce - ANR-17-ROSE-0001
Cibler le métabolisme des fibroblastes adventitiels activés pour traiter l'hypertension pulmonaire - ANR-20-CE14-0006
Guerre bactérienne: Architecture et Fonction du Système de Sécrétion de Type VI - ANR-14-CE14-0006
Bloc-outil et Imagerie de Précision pour le Binage Intra-rang Précoce - ANR-17-ROSE-0001
Cibler le métabolisme des fibroblastes adventitiels activés pour traiter l'hypertension pulmonaire - ANR-20-CE14-0006